Hepatocellular carcinoma (HCC) is the primary malignancy of the liver, which appears to be rising in incidence in the United States and other developed western countries. The prevalence of HCC worldwide parallels that of viral hepatitis, and the majority of cases are associated with hepatitis B (HBV) and hepatitis C (HCV). It has been observed that patients with longstanding chronic hepatitis or cirrhosis who have hepatitis B, C, or hereditary hemochromatosis have the highest risk of developing HCC. Patients with longstanding alcoholic cirrhosis are also at risk for developing this type of malignancy.
Diagnosis of hepatocellular carcinoma is, however, extremely challenging as most of the patients who are developing HCC have no symptoms other than those related to their longstanding liver disease. Once symptoms such as abdominal pain, weight loss, early satiety, jaundice and a palpable mass in the upper abdomen, have developed, HCC has most likely advanced to a stage that is too late for an effective treatment. As a result, the current median survival following diagnosis is only about 6 to 20 months.
The current clinical methods are in some ways ineffective for early diagnosis of HCC. Most HCCs are first suspected based on the imaging results of computerized axial tomography (CAT) scans or ultrasound scans. However, liver imaging has a high false positive rate due to low sensitivity and specificity. Accordingly, the diagnosis often has to be confirmed by performing an invasive needle biopsy.
Another commonly used diagnostic method is based on the blood level of alpha-fetoprotein (AFP), a normal serum protein synthesized by fetal liver cells. It is often measured as a part of screening in patients with chronic hepatitis B or chronic hepatitis C and cirrhosis. Since there is a good correlation between elevated levels of AFP and the occurrence of HCC, determination of AFP levels is often included as a serum marker of the disease. However, AFP as a sole indicator of HCC is often of very limited value for diagnosing HCC, since elevated AFP levels are not specific for HCC. Further complications come from that fact that not all HCC patients exhibit an elevated level of AFP. In fact, it has been shown that only about 70% of patients with HCC have elevated AFP levels.
As such, there is a need for an improved diagnostic assay for early detection of HCC. Accordingly, the present invention relates to an assay that exhibits a strong correlation between the level of GP73-specific autoantibodies and HCC, which can be used as a biological marker for monitoring and diagnosis of HCC.